An imidate moiety is strongly electrophilic, and as such, represents an important functional group in organic synthesis. The imidate moiety can be transformed into a wide variety of products, by virtue of undergoing reaction with a large number of nucleophiles. In addition, the imidate moiety can serve as a free radical scavenger. For example, ethyl 3,4,5-trihydroxybenzimidate blocks free radical generation from NADPH oxidase. This free radical scavenging activity decreases the amount of tissue damage, such as limiting damage to the heart following an infarction or other ischemic episode.
The use of aryl imidates in the preparation of thiazoles, or when reduced, thiazolines and thiazolidines, is of particular interest. Compounds such as desferrithiocin and structural analogues contain a thiazoline ring, and these compounds represent an advance in iron chelation therapy for subjects suffering from iron overload diseases. Present therapeutic agents such as desferrioxamine require parenteral administration and have a very short half-life in the body, so that patient compliance and treatment cost are serious problems for subjects receiving long-term chelation therapy. Desferrithiocin and related compounds are effective when orally administered, thereby reducing patient compliance issues.
Unfortunately, ethyl 2,4-dihydroxybenzimidate, which is a precursor to the potent, less toxic form of desferrithiocin known as 4′-hydroxydesazadesferrithiocin, remains a synthetic challenge. At this time, alkyl 2,4-dihydroxybenzimidates are not commercially available. Therefore, there is a need for novel methods of producing alkyl 2,4-dihydroxybenzimidate at a reasonable cost.